atherogenesis Flashcards
What are the non-modifiable risk factors for arterial disease?
The non-modifiable risk factors for arterial disease include genetic abnormalities, family history, increasing age, and being male.
What are the modifiable risk factors for arterial disease?
The modifiable risk factors for arterial disease include smoking, high blood pressure (hypertension), high cholesterol levels, and diabetes mellitus.
How does smoking contribute to atherogenesis?
Smoking damages the lining of the blood vessels, leading to the accumulation of plaque and the development of atherosclerosis.
How does high blood pressure (hypertension) contribute to atherogenesis?
High blood pressure damages the blood vessels’ lining and promotes atherosclerosis development by increasing the pressure on the arterial walls.
How do high cholesterol levels contribute to atherogenesis?
High levels of LDL cholesterol in the blood can lead to the formation of plaque in the arterial walls, which can eventually cause atherosclerosis.
How does diabetes mellitus contribute to atherogenesis?
Diabetes mellitus can lead to high levels of glucose in the blood, which can damage the arterial walls and promote the development of atherosclerosis.
What is the lipid hypothesis?
The lipid hypothesis suggests that there is a correlation between a low cholesterol diet and a low incidence of cardiovascular disease. Cardiovascular disease is linked to smoking, hypertension, and high blood cholesterol, specifically high LDL cholesterol.
What did Brown and Goldstein discover about macrophages and cholesterol?
Brown and Goldstein discovered that macrophages typically take up small amounts of LDL, but patients with LDL receptor deficiency accumulate large amounts of cholesterol in their macrophages. They also found that circulating LDL must be modified to become atherogenic, leading to increased LDL uptake via scavenger receptors.
What is the lipid oxidation hypothesis?
The lipid oxidation hypothesis suggests that atherosclerosis results from free-radical-driven oxidation modification of LDL-cholesterol by substances such as hydroxyl radical, superoxide, and singlet oxygen. Modified LDL is taken up more rapidly by macrophages through non-specific scavenger receptors.
Is lipid oxidation the primary cause of atherosclerosis?
No, lipid oxidation is not the primary cause of atherosclerosis. While it is a contributing factor, it is not the only factor, and other hypotheses, such as the response to injury hypothesis, also play a role in the development of atherosclerosis.
What is the response to injury hypothesis?
The response to injury hypothesis suggests that atherosclerosis is initiated by an injury to the arterial wall, which triggers a series of events that lead to the accumulation of lipids and the formation of atherosclerotic plaques.
What are the steps in the response to injury hypothesis?
The steps in the response to injury hypothesis include endothelial injury/dysfunction, lipoprotein accumulation, leukocyte adhesion and migration, lipid accumulation (foam cells), smooth muscle recruitment and proliferation, and extracellular matrix formation.
What can cause endothelial injury/dysfunction?
Endothelial injury/dysfunction can be caused by haemodynamic stress (high blood pressure, arterial branch points), toxins (e.g., cigarette smoke), hyperlipidaemia, and ageing.
What is the endothelial injury response?
The endothelial injury response involves the release of cytokines and the expression of adhesion molecules by endothelial cells, allowing leukocytes (monocytes) to bind and infiltrate (macrophages). Injury leads to reduced NO production.
What are some small molecules involved in atherosclerosis?
Some small molecules involved in atherosclerosis include cytokines, growth factors, chemokines, and adhesion molecules. Cytokines are small protein molecules that mediate/regulate inflammatory responses, such as IL-1, TNF-a, and IFN-y. Growth factors stimulate the growth of specific cell lines, such as PDGF and VSMGF. Chemokines attract monocytes, such as MCP1, and adhesion molecules include ICAM-1 and VCAM-1.
